📚 Article Archive

Anthocyanins inhibit lipogenesis during adipocyte differentiation of 3T3-L1 preadipocytes.

Bonggi Lee, Minsup Lee, Michael Lefevre +1 more · 2014 · Plant foods for human nutrition (Dordrecht, Netherlands) · Springer · added 2026-04-24

Bonggi Lee, Minsup Lee, Michael Lefevre, Hyeung-Rak Kim Show less

Anthocyanins have been shown to suppress body weight and fat mass in animal studies. However, the effect of anthocyanins on the process of lipid accumulation during adipocyte differentiation is not fu Show more

Anthocyanins have been shown to suppress body weight and fat mass in animal studies. However, the effect of anthocyanins on the process of lipid accumulation during adipocyte differentiation is not fully understood and the lipogenic transcription factors regulated by anthocyanins have not been identified. We investigated the effects of anthocyanins on lipogenesis pathways during adipocyte differentiation in 3T3-L1 cells. Anthocyanins reduced triglyceride (TG) accumulation in a dose-dependent manner during adipocyte differentiation. Accumulation of TG was rapidly reversed by anthocyanin withdrawal. Anthocyanins markedly reduced gene and protein expression levels of lipogenic transcription factors such as liver X receptor α, sterol regulatory element-binding protein-1c, peroxisome proliferators-activated receptor-γ, and CCAAT enhancer-binding protein-α. In addition, the target gene and protein expression of these lipogenic transcription factors such as fatty acid synthase, stearoyl-CoA desaturase-1, and acetyl-CoA carboxylase α were markedly suppressed by anthocyanins. Thus, anthocyanins suppress lipid accumulation in adipocytes due to broad inhibition of the transcription factors regulating lipogenesis. This may partially explain the mechanism by which anthocyanins exert their anti-obesity effect. Show less

no PDF DOI: 10.1007/s11130-014-0407-z

NR1H3

Reciprocal regulation of LXRα activity by ASXL1 and ASXL2 in lipogenesis.

Ui-Hyun Park, Mi-ran Seong, Eun-Joo Kim +4 more · 2014 · Biochemical and biophysical research communications · Elsevier · added 2026-04-24

Ui-Hyun Park, Mi-ran Seong, Eun-Joo Kim, Wonhee Hur, Sung Woo Kim, Seung Kew Yoon, Soo-Jong Um Show less

Liver X receptor alpha (LXRα), a member of the nuclear receptor superfamily, plays a pivotal role in hepatic cholesterol and lipid metabolism, regulating the expression of genes associated with hepati Show more

Liver X receptor alpha (LXRα), a member of the nuclear receptor superfamily, plays a pivotal role in hepatic cholesterol and lipid metabolism, regulating the expression of genes associated with hepatic lipogenesis. The additional sex comb-like (ASXL) family was postulated to regulate chromatin function. Here, we investigate the roles of ASXL1 and ASXL2 in regulating LXRα activity. We found that ASXL1 suppressed ligand-induced LXRα transcriptional activity, whereas ASXL2 increased LXRα activity through direct interaction in the presence of the ligand. Chromatin immunoprecipitation (ChIP) assays showed ligand-dependent recruitment of ASXLs to ABCA1 promoters, like LXRα. Knockdown studies indicated that ASXL1 inhibits, while ASXL2 increases, lipid accumulation in H4IIE cells, similar to their roles in transcriptional regulation. We also found that ASXL1 expression increases under fasting conditions, and decreases in insulin-treated H4IIE cells and the livers of high-fat diet-fed mice. Overall, these results support the reciprocal role of the ASXL family in lipid homeostasis through the opposite regulation of LXRα. Show less

no PDF DOI: 10.1016/j.bbrc.2013.11.124

NR1H3

Ursodeoxycholic acid inhibits liver X receptor α-mediated hepatic lipogenesis via induction of the nuclear corepressor SMILE.

Ji-Min Lee, Gil-Tae Gang, Don-Kyu Kim +4 more · 2014 · The Journal of biological chemistry · American Society for Biochemistry and Molecular Biology · added 2026-04-24

Ji-Min Lee, Gil-Tae Gang, Don-Kyu Kim, Yong Deuk Kim, Seung-Hoi Koo, Chul-Ho Lee, Hueng-Sik Choi Show less

Small heterodimer partner interacting leucine zipper protein (SMILE) has been identified as a nuclear corepressor of the nuclear receptor (NRs) family. Here, we examined the role of SMILE in the regul Show more

Small heterodimer partner interacting leucine zipper protein (SMILE) has been identified as a nuclear corepressor of the nuclear receptor (NRs) family. Here, we examined the role of SMILE in the regulation of nuclear receptor liver X receptor (LXR)-mediated sterol regulatory element binding protein-1c (SREBP-1c) gene expression. We found that SMILE inhibited T0901317 (T7)-induced transcriptional activity of LXR, which functions as a major regulator of lipid metabolism by inducing SREBP-1c, fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) gene expression. Moreover, we demonstrated that SMILE physically interacts with LXR and represses T7-induced LXR transcriptional activity by competing with coactivator SRC-1. Adenoviral overexpression of SMILE (Ad-SMILE) attenuated fat accumulation and lipogenic gene induction in the liver of T7 administered or of high fat diet (HFD)-fed mice. Furthermore, we investigated the mechanism by which ursodeoxycholic acid (UDCA) inhibits LXR-induced lipogenic gene expression. Interestingly, UDCA treatment significantly increased SMILE promoter activity and gene expression in an adenosine monophosphate-activated kinase-dependent manner. Furthermore, UDCA treatment repressed T7-induced SREBP-1c, FAS, and ACC protein levels, whereas knockdown of endogenous SMILE gene expression by adenovirus SMILE shRNA (Ad-shSMILE) significantly reversed UDCA-mediated repression of SREBP-1c, FAS, and ACC protein levels. Collectively, these results demonstrate that UDCA activates SMILE gene expression through adenosine monophosphate-activated kinase phosphorylation, which leads to repression of LXR-mediated hepatic lipogenic enzyme gene expression. Show less

no PDF DOI: 10.1074/jbc.M113.491522

NR1H3

DIRAS3 regulates the autophagosome initiation complex in dormant ovarian cancer cells.

Zhen Lu, Maria T Baquero, Hailing Yang +7 more · 2014 · Autophagy · added 2026-04-24

Zhen Lu, Maria T Baquero, Hailing Yang, Maojie Yang, Albert S Reger, Choel Kim, Douglas A Levine, Charlotte H Clarke, Warren S-L Liao, Robert C Bast Show less

DIRAS3 is an imprinted tumor suppressor gene that is downregulated in 60% of human ovarian cancers. Re-expression of DIRAS3 at physiological levels inhibits proliferation, decreases motility, induces Show more

DIRAS3 is an imprinted tumor suppressor gene that is downregulated in 60% of human ovarian cancers. Re-expression of DIRAS3 at physiological levels inhibits proliferation, decreases motility, induces autophagy, and regulates tumor dormancy. Functional inhibition of autophagy with choroquine in dormant xenografts that express DIRAS3 significantly delays tumor regrowth after DIRAS3 levels are reduced, suggesting that autophagy sustains dormant ovarian cancer cells. This study documents a newly discovered role for DIRAS3 in forming the autophagosome initiation complex (AIC) that contains BECN1, PIK3C3, PIK3R4, ATG14, and DIRAS3. Participation of BECN1 in the AIC is inhibited by binding of BECN1 homodimers to BCL2. DIRAS3 binds BECN1, disrupting BECN1 homodimers and displacing BCL2. Binding of DIRAS3 to BECN1 increases the association of BECN1 with PIK3C3 and ATG14, facilitating AIC activation. Amino acid starvation of cells induces DIRAS3 expression, reduces BECN1-BCL2 interaction and promotes autophagy, whereas DIRAS3 depletion blocks amino acid starvation-induced autophagy. In primary ovarian cancers, punctate expression of DIRAS3, BECN1, and the autophagic biomarker MAP1LC3 are highly correlated (P<0.0001), underlining the clinical relevance of these mechanistic studies. Punctate expression of DIRAS3 and MAP1LC3 was detected in only 21-23% of primary ovarian cancers but in 81-84% of tumor nodules found on the peritoneal surface at second-look operations following primary chemotherapy. This reflects a 4-fold increase (P<0.0001) in autophagy between primary disease and post-treatment recurrence. We suggest that DIRAS3 not only regulates the AIC, but induces autophagy in dormant, nutrient-deprived ovarian cancer cells that remain after conventional chemotherapy, facilitating their survival. Show less

no PDF DOI: 10.4161/auto.28577

PIK3C3

A pepper MSRB2 gene confers drought tolerance in rice through the protection of chloroplast-targeted genes.

Joung Sug Kim, Hyang-Mi Park, Songhwa Chae +10 more · 2014 · PloS one · PLOS · added 2026-04-24

Joung Sug Kim, Hyang-Mi Park, Songhwa Chae, Tae-Ho Lee, Duk-Ju Hwang, Sung-Dug Oh, Jong-Sug Park, Dae-Geun Song, Cheol-Ho Pan, Doil Choi, Yul-Ho Kim, Baek Hie Nahm, Yeon-Ki Kim Show less

The perturbation of the steady state of reactive oxygen species (ROS) due to biotic and abiotic stresses in a plant could lead to protein denaturation through the modification of amino acid residues, Show more

The perturbation of the steady state of reactive oxygen species (ROS) due to biotic and abiotic stresses in a plant could lead to protein denaturation through the modification of amino acid residues, including the oxidation of methionine residues. Methionine sulfoxide reductases (MSRs) catalyze the reduction of methionine sulfoxide back to the methionine residue. To assess the role of this enzyme, we generated transgenic rice using a pepper CaMSRB2 gene under the control of the rice Rab21 (responsive to ABA protein 21) promoter with/without a selection marker, the bar gene. A drought resistance test on transgenic plants showed that CaMSRB2 confers drought tolerance to rice, as evidenced by less oxidative stress symptoms and a strengthened PSII quantum yield under stress conditions, and increased survival rate and chlorophyll index after the re-watering. The results from immunoblotting using a methionine sulfoxide antibody and nano-LC-MS/MS spectrometry suggest that porphobilinogen deaminase (PBGD), which is involved in chlorophyll synthesis, is a putative target of CaMSRB2. The oxidized methionine content of PBGD expressed in E. coli increased in the presence of H2O2, and the Met-95 and Met-227 residues of PBGD were reduced by CaMSRB2 in the presence of dithiothreitol (DTT). An expression profiling analysis of the overexpression lines also suggested that photosystems are less severely affected by drought stress. Our results indicate that CaMSRB2 might play an important functional role in chloroplasts for conferring drought stress tolerance in rice. Show less

no PDF DOI: 10.1371/journal.pone.0090588

RAB21

High glucose alters Cx43 expression and gap junction intercellular communication in retinal Müller cells: promotes Müller cell and pericyte apoptosis.

Tetsuya Muto, Thomas Tien, Dongjoon Kim +2 more · 2014 · Investigative ophthalmology & visual science · added 2026-04-24

Tetsuya Muto, Thomas Tien, Dongjoon Kim, Vijay P Sarthy, Sayon Roy Show less

To investigate whether high glucose (HG) alters connexin 43 (Cx43) expression and gap junction intercellular communication (GJIC) activity in retinal Müller cells, and promotes Müller cell and pericyt Show more

To investigate whether high glucose (HG) alters connexin 43 (Cx43) expression and gap junction intercellular communication (GJIC) activity in retinal Müller cells, and promotes Müller cell and pericyte loss. Retinal Müller cells (rMC-1) and cocultures of rMC-1 and retinal pericytes were grown in normal (N) or HG (30 mM glucose) medium. Additionally, rMC-1 transfected with Cx43 small interfering RNA (siRNA) were grown as cocultures with pericytes, and rMC-1 transfected with Cx43 plasmid were grown in HG. Expression of Cx43 was determined by Western blotting and immunostaining and GJIC was assessed by scrape-loading dye transfer (SLDT) technique. Apoptosis was analyzed by TUNEL or differential staining assay, and Akt activation by assessing Akt phosphorylation. In monocultures of rMC-1 and cocultures of rMC-1 and pericytes, Cx43 protein level, number of Cx43 plaques, GJIC, and Akt phosphorylation were significantly reduced in HG medium. Number of TUNEL-positive cells was also significantly increased in rMC-1 monocultures and in rMC-1 and pericyte cocultures grown in HG medium. Importantly, when rMC-1 transfected with Cx43 siRNA were grown as cocultures with pericytes, a significant decrease in GJIC, and increase in TUNEL-positive cells was observed, concomitant with decreased Akt phosphorylation. Upregulation of Cx43 rescued rMC-1 from HG-induced apoptosis. Gap junction communication between Müller cells and pericytes is essential for their survival. Downregulation of Cx43 that is HG induced and impairment of GJIC activity in Müller cells contributes to loss of glial and vascular cells associated with the pathogenesis of diabetic retinopathy. Show less

no PDF DOI: 10.1167/iovs.14-14606

RMC1

A novel glucagon-related peptide (GCRP) and its receptor GCRPR account for coevolution of their family members in vertebrates.

Cho Rong Park, Mi Jin Moon, Sumi Park +5 more · 2013 · PloS one · PLOS · added 2026-04-24

Cho Rong Park, Mi Jin Moon, Sumi Park, Dong-Kyu Kim, Eun Bee Cho, Robert Peter Millar, Jong-Ik Hwang, Jae Young Seong Show less

The glucagon (GCG) peptide family consists of GCG, glucagon-like peptide 1 (GLP1), and GLP2, which are derived from a common GCG precursor, and the glucose-dependent insulinotropic polypeptide (GIP). Show more

The glucagon (GCG) peptide family consists of GCG, glucagon-like peptide 1 (GLP1), and GLP2, which are derived from a common GCG precursor, and the glucose-dependent insulinotropic polypeptide (GIP). These peptides interact with cognate receptors, GCGR, GLP1R, GLP2R, and GIPR, which belong to the secretin-like G protein-coupled receptor (GPCR) family. We used bioinformatics to identify genes encoding a novel GCG-related peptide (GCRP) and its cognate receptor, GCRPR. The GCRP and GCRPR genes were found in representative tetrapod taxa such as anole lizard, chicken, and Xenopus, and in teleosts including medaka, fugu, tetraodon, and stickleback. However, they were not present in mammals and zebrafish. Phylogenetic and genome synteny analyses showed that GCRP emerged through two rounds of whole genome duplication (2R) during early vertebrate evolution. GCRPR appears to have arisen by local tandem gene duplications from a common ancestor of GCRPR, GCGR, and GLP2R after 2R. Biochemical ligand-receptor interaction analyses revealed that GCRP had the highest affinity for GCRPR in comparison to other GCGR family members. Stimulation of chicken, Xenopus, and medaka GCRPRs activated Gαs-mediated signaling. In contrast to chicken and Xenopus GCRPRs, medaka GCRPR also induced Gαq/11-mediated signaling. Chimeric peptides and receptors showed that the K(16)M(17)K(18) and G(16)Q(17)A(18) motifs in GCRP and GLP1, respectively, may at least in part contribute to specific recognition of their cognate receptors through interaction with the receptor core domain. In conclusion, we present novel data demonstrating that GCRP and GCRPR evolved through gene/genome duplications followed by specific modifications that conferred selective recognition to this ligand-receptor pair. Show less

📄 PDF DOI: 10.1371/journal.pone.0065420

GIPR

Resistin knockout mice exhibit impaired adipocyte glucose-dependent insulinotropic polypeptide receptor (GIPR) expression.

Su-Jin Kim, Cuilan Nian, Christopher H S McIntosh · 2013 · Diabetes · added 2026-04-24

Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone that also plays a regulatory role in fat metabolism. In 3T3-L1 cells, resistin was demonstrated to be a key mediator of GIP st Show more

Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone that also plays a regulatory role in fat metabolism. In 3T3-L1 cells, resistin was demonstrated to be a key mediator of GIP stimulation of lipoprotein lipase (LPL) activity, involving activation of protein kinase B (PKB) and reduced phosphorylation of liver kinase B1 (LKB1) and AMP-activated protein kinase (AMPK). The current study was initiated to determine whether resistin has additional roles in GIP-regulated adipocyte functions. Analysis of primary adipocytes isolated from Retn(-/-), Retn(+/-), and Retn(+/+) mice found that GIP stimulated the PKB/LKB1/AMPK/LPL pathway and fatty acid uptake only in Retn(+/+) adipocytes, suggesting that GIP signaling and/or GIP responsiveness were compromised in Retn(+/-) and Retn(-/-) adipocytes. GIP receptor (GIPR) protein and mRNA were decreased in Retn(+/-) and Retn(-/-) adipocytes, but resistin treatment rescued LPL responsiveness to GIP. In addition, genes encoding tumor necrosis factor (TNF), TNF receptor 2 (TNFR2), and the signaling proteins stress-activated protein kinase (SAPK)/Jun NH(2)-terminal kinase (JNK), were downregulated, and phosphorylated levels of SAPK/JNK/c-Jun were decreased in Retn(-/-) mice. Chromatin immunoprecipitation assays were used to identify a 12-O-tetradecanoylphorbol-13-acetate (TPA)-response element (TRE-III) responsible for c-Jun-mediated transcriptional activation of Gipr. Blunted GIP responsiveness in Retn(+/-) and Retn(-/-) adipocytes was therefore largely due to the greatly reduced GIPR expression associated with decreased c-Jun-mediated transcriptional activation of Gipr. Show less

📄 PDF DOI: 10.2337/db12-0257

GIPR

Upregulation of adenylate cyclase 3 (ADCY3) increases the tumorigenic potential of cells by activating the CREB pathway.

Seung-Hyun Hong, Sung-Ho Goh, Sang Jin Lee +12 more · 2013 · Oncotarget · Impact Journals · added 2026-04-24

Seung-Hyun Hong, Sung-Ho Goh, Sang Jin Lee, Jung-Ah Hwang, Jieun Lee, Il-Ju Choi, Hyehyun Seo, Jong-Hoon Park, Hiromu Suzuki, Eiichiro Yamamoto, In-Hoo Kim, Jin Sook Jeong, Mi Ha Ju, Dong-Hee Lee, Yeon-Su Lee Show less

Adenylate cyclase 3 (ADCY3) is a widely expressed membrane-associated protein in human tissues, which catalyzes the formation of cyclic adenosine-3',5'-monophosphate (cAMP). However, our transcriptome Show more

Adenylate cyclase 3 (ADCY3) is a widely expressed membrane-associated protein in human tissues, which catalyzes the formation of cyclic adenosine-3',5'-monophosphate (cAMP). However, our transcriptome analysis of gastric cancer tissue samples (NCBI GEO GSE30727) revealed that ADCY3 expression was specifically altered in cancer samples. Here we investigated the tumor-promoting effects of ADCY3 overexpression and confirmed a significant correlation between the upregulation of ADCY3 and Lauren's intestinal-type gastric cancers. ADCY3 overexpression increased cell migration, invasion, proliferation, and clonogenicity in HEK293 cells; conversely, silencing ADCY3 expression in SNU-216 cells reduced these phenotypes. Interestingly, ADCY3 overexpression increased both the mRNA level and activity of matrix metalloproteinase 2 (MMP2) and MMP9 by increasing the levels of cAMP and phosphorylated cAMP-responsive element-binding protein (CREB). Consistent with these findings, treatment with a protein kinase A (PKA) inhibitor decreased MMP2 and MMP9 expression levels in ADCY3-overexpressing cells. Knockdown of ADCY3 expression by stable shRNA in human gastric cancer cells suppressed tumor growth in a tumor xenograft model. Thus, ADCY3 overexpression may exert its tumor-promoting effects via the cAMP/PKA/CREB pathway. Additionally, bisulfite sequencing of the ADCY3 promoter region revealed that gene expression was reduced by hypermethylation of CpG sites, and increased by 5-Aza-2'-deoxycytidine (5-Aza-dC)-induced demethylation. Our study is the first to report an association of ADCY3 with gastric cancer as well as its tumorigenic potentials. In addition, we demonstrate that the expression of ADCY3 is regulated through an epigenetic mechanism. Further study on the mechanism of ADCY3 in tumorigenesis will provide the basis as a new molecular target of gastric cancer. Show less

📄 PDF DOI: 10.18632/oncotarget.1324

ADCY3

Apolipoprotein A-IV as a novel gene associated with polycystic ovary syndrome.

Yong-Soo Kim, Bon-Hee Gu, Bum-Chae Choi +6 more · 2013 · International journal of molecular medicine · added 2026-04-24

Yong-Soo Kim, Bon-Hee Gu, Bum-Chae Choi, Myung-Sun Kim, Sangjin Song, Ji-Hyun Yun, Mi Kyung Chung, Cheol-Hee Choi, Kwang-Hyun Baek Show less

Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic disorder, affecting 6-10% of women of reproductive age. The etiology remains poorly understood. To investigate the differentially expre Show more

Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic disorder, affecting 6-10% of women of reproductive age. The etiology remains poorly understood. To investigate the differentially expressed proteins from PCOS patients versus healthy women, the protein expression in follicular fluid was analyzed using two-dimensional electrophoresis (2-DE). Since follicular fluid contains a number of secretory proteins required for oocyte fertilization and follicle maturation, it is possible that follicular fluid can be used as a provisional source for identifying pivotal proteins associated with PCOS. In this study, six overexpressed proteins [kininogen 1, cytokeratin 9, antithrombin, fibrinogen γ-chain, apolipoprotein A-IV (apoA-IV) precursor and α-1-B-glycoprotein (A1BG)] in follicular fluids from PCOS patients were identified with matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS) and nano LC-MS/MS. Western blot analysis confirmed that the protein expression levels of apoA-IV precursor and A1BG were increased in follicular fluid from PCOS patients compared with those from normal controls. The analysis of protein expression for other proteins revealed individual variation. These results facilitate the understanding of the molecular mechanisms of PCOS and provide candidate biomarkers for the development of diagnostic and therapeutic tools. Show less

no PDF DOI: 10.3892/ijmm.2013.1250

APOA4

Identification and characterization of cyclic AMP response element-binding protein H response element in the human apolipoprotein A5 gene promoter.

Kwang Hoon Song, Ah-Yeon Park, Ji-Eun Kim +1 more · 2013 · BioMed research international · added 2026-04-24

Kwang Hoon Song, Ah-Yeon Park, Ji-Eun Kim, Jin Yeul Ma Show less

The cyclic AMP response element-binding protein H (CREBH) plays important roles in hepatic lipogenesis, fatty acid oxidation, and lipolysis under metabolic stress. Here, we report CREBH as a novel reg Show more

The cyclic AMP response element-binding protein H (CREBH) plays important roles in hepatic lipogenesis, fatty acid oxidation, and lipolysis under metabolic stress. Here, we report CREBH as a novel regulator of human APOA5. Knockdown of endogenous CREBH expression via small interfering RNA resulted in the downregulation of human APOA5 mRNA expression in human hepatoma cells, HepG2. Sequence analysis suggested that putative CREBH response element (CREBHRE) is located in the human APOA5 promoter region and is highly conserved in both human and rodent. To clarify whether the human APOA5 promoter is regulated by CREBH, we analyzed the human APOA5 promoter region using a transient transfection assay and determined that transfection of CREBH induced human APOA5 promoter activity. Moreover, it was shown that CREBH directly regulated human APOA5 gene expression by binding to a unique CREBHRE located in the proximal human APOA5 promoter region, using 5'-deletion and mutagenesis of human APOA5 promoter analysis and chromatin immunoprecipitation assay. Taken together, our results demonstrated that human APOA5 is directly regulated by CREBH via CREBHRE and provided a new insight into the role of this liver-specific bZIP transcription factor in lipoprotein metabolism and triglyceride homeostasis. Show less

📄 PDF DOI: 10.1155/2013/892491

APOA5

Trans-ethnic fine-mapping of lipid loci identifies population-specific signals and allelic heterogeneity that increases the trait variance explained.

Ying Wu, Lindsay L Waite, Anne U Jackson +74 more · 2013 · PLoS genetics · PLOS · added 2026-04-24

Ying Wu, Lindsay L Waite, Anne U Jackson, Wayne H-H Sheu, Steven Buyske, Devin Absher, Donna K Arnett, Eric Boerwinkle, Lori L Bonnycastle, Cara L Carty, Iona Cheng, Barbara Cochran, Damien C Croteau-Chonka, Logan Dumitrescu, Charles B Eaton, Nora Franceschini, Xiuqing Guo, Brian E Henderson, Lucia A Hindorff, Eric Kim, Leena Kinnunen, Pirjo Komulainen, Wen-Jane Lee, Loic Le Marchand, Yi Lin, Jaana Lindström, Oddgeir Lingaas-Holmen, Sabrina L Mitchell, Narisu Narisu, Jennifer G Robinson, Fred Schumacher, Alena Stančáková, Jouko Sundvall, Yun-Ju Sung, Amy J Swift, Wen-Chang Wang, Lynne Wilkens, Tom Wilsgaard, Alicia M Young, Linda S Adair, Christie M Ballantyne, Petra Bůžková, Aravinda Chakravarti, Francis S Collins, David Duggan, Alan B Feranil, Low-Tone Ho, Yi-Jen Hung, Steven C Hunt, Kristian Hveem, Jyh-Ming J Juang, Antero Y Kesäniemi, Johanna Kuusisto, Markku Laakso, Timo A Lakka, I-Te Lee, Mark F Leppert, Tara C Matise, Leena Moilanen, Inger Njølstad, Ulrike Peters, Thomas Quertermous, Rainer Rauramaa, Jerome I Rotter, Jouko Saramies, Jaakko Tuomilehto, Matti Uusitupa, Tzung-Dau Wang, Michael Boehnke, Christopher A Haiman, Yii-Der I Chen, Charles Kooperberg, Themistocles L Assimes, Dana C Crawford, Chao A Hsiung, Kari E North, Karen L Mohlke Show less

Genome-wide association studies (GWAS) have identified ~100 loci associated with blood lipid levels, but much of the trait heritability remains unexplained, and at most loci the identities of the trai Show more

Genome-wide association studies (GWAS) have identified ~100 loci associated with blood lipid levels, but much of the trait heritability remains unexplained, and at most loci the identities of the trait-influencing variants remain unknown. We conducted a trans-ethnic fine-mapping study at 18, 22, and 18 GWAS loci on the Metabochip for their association with triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), respectively, in individuals of African American (n = 6,832), East Asian (n = 9,449), and European (n = 10,829) ancestry. We aimed to identify the variants with strongest association at each locus, identify additional and population-specific signals, refine association signals, and assess the relative significance of previously described functional variants. Among the 58 loci, 33 exhibited evidence of association at P<1 × 10(-4) in at least one ancestry group. Sequential conditional analyses revealed that ten, nine, and four loci in African Americans, Europeans, and East Asians, respectively, exhibited two or more signals. At these loci, accounting for all signals led to a 1.3- to 1.8-fold increase in the explained phenotypic variance compared to the strongest signals. Distinct signals across ancestry groups were identified at PCSK9 and APOA5. Trans-ethnic analyses narrowed the signals to smaller sets of variants at GCKR, PPP1R3B, ABO, LCAT, and ABCA1. Of 27 variants reported previously to have functional effects, 74% exhibited the strongest association at the respective signal. In conclusion, trans-ethnic high-density genotyping and analysis confirm the presence of allelic heterogeneity, allow the identification of population-specific variants, and limit the number of candidate SNPs for functional studies. Show less

📄 PDF DOI: 10.1371/journal.pgen.1003379

APOA5

Association of apolipoprotein A-V concentration with apolipoprotein A5 gene -1131T>C polymorphism and fasting triglyceride levels.

Jin Young Kim, Oh Yoen Kim, Jean Kyung Paik +2 more · 2013 · Journal of clinical lipidology · Elsevier · added 2026-04-24

Jin Young Kim, Oh Yoen Kim, Jean Kyung Paik, Sang-Hyun Lee, Jong Ho Lee Show less

The relationship between the apolipoprotein A5 gene (APOA5) -1131T>C polymorphism and triglyceride levels is well established, but the association between circulating apolipoprotein A-V (apoA-V) conce Show more

The relationship between the apolipoprotein A5 gene (APOA5) -1131T>C polymorphism and triglyceride levels is well established, but the association between circulating apolipoprotein A-V (apoA-V) concentrations and APOA5 -1131T>C genotypes and triglyceride levels remains controversial. Normotriglyceridemic controls (n = 1526) and hypertriglyceridemic cases (n = 744) were genotyped for APOA5-1131T>C. ApoA-V, triglycerides, insulin, free fatty acids, and lipoprotein profiles were analyzed. APOA5-1131C minor allele frequency was significantly greater in hypertriglyceridemic patients than normotriglyceridemic controls. ApoA-V concentrations were not significantly different between controls and cases. Normotriglyceridemic controls with T/C and C/C showed lower apoA-V concentrations (14% and 27%, respectively), than did T/T controls. Similar genotypic effects on apoA-V were found in hypertriglyceridemic cases. In both groups, APOA5-1131T>C was associated with higher triglycerides, smaller LDL particle size, and lower HDL-cholesterol. We observed a negative correlation between apoA-V and triglyceride in controls and a positive correlation in hypertriglyceridemic patients, regardless of genotype. We observed a positive correlation between apoA-V and free fatty acids in both groups, regardless of genotype, and a positive correlation between apoA-V and HDL-cholesterol in controls (T/T, T/C, or C/C) and hypertriglyceridemic patients (T/T or T/C). APOA5-1131C may lead to reduced apoA-V with concomitantly reduced lipoprotein lipase activation, resulting in greater serum triglycerides, although the correlation between apoA-V and triglyceride was reversed when triglyceride was greater than 150 mg/dL. Show less

no PDF DOI: 10.1016/j.jacl.2012.06.002

APOA5

Anti-proliferative activity of hydnocarpin, a natural lignan, is associated with the suppression of Wnt/β-catenin signaling pathway in colon cancer cells.

Min-Ai Lee, Won Kyung Kim, Hyen Joo Park +2 more · 2013 · Bioorganic & medicinal chemistry letters · Elsevier · added 2026-04-24

Min-Ai Lee, Won Kyung Kim, Hyen Joo Park, Sam Sik Kang, Sang Kook Lee Show less

Based on the Wnt inhibitors as potential targets in the development of anticancer agents, natural compounds were evaluated for β-catenin-mediated transcriptional activity. A natural lignan hydnocarpin Show more

Based on the Wnt inhibitors as potential targets in the development of anticancer agents, natural compounds were evaluated for β-catenin-mediated transcriptional activity. A natural lignan hydnocarpin isolated from Lonicera japonica was considered a potential inhibitor for Wnt/β-catenin signalings. The anti-proliferative activity of hydnocarpin was also found to be associated with the suppression of Wnt/β-catenin-mediated signaling pathway in human colon cancer cells. These data suggest that hydnocarpin might be a novel Wnt inhibitor and has a potential of signaling regulator in β-catenin-mediated signaling pathways. Show less

no PDF DOI: 10.1016/j.bmcl.2013.08.065

AXIN1

Axin expression enhances herpes simplex virus type 1 replication by inhibiting virus-mediated cell death in L929 cells.

Eun-Jin Choi, Sewoon Kim, Eek-hoon Jho +2 more · 2013 · The Journal of general virology · added 2026-04-24

Eun-Jin Choi, Sewoon Kim, Eek-hoon Jho, Ki-Joon Song, Sun-Ho Kee Show less

Herpes simplex virus type 1 (HSV-1) replicates in various cell types and induces early cell death, which limits viral replication in certain cell types. Axin is a scaffolding protein that regulates Wn Show more

Herpes simplex virus type 1 (HSV-1) replicates in various cell types and induces early cell death, which limits viral replication in certain cell types. Axin is a scaffolding protein that regulates Wnt signalling and participates in various cellular events, including cellular proliferation and cell death. The effects of axin expression on HSV-1 infection were investigated based on our initial observation that Wnt3a treatment or axin knockdown reduced HSV-1 replication. L929 cells expressed the axin protein in a doxycycline-inducible manner (L-axin) and enhanced HSV-1 replication in comparison to control cells (L-EV). HSV-1 infection induced cell death as early as 6 h after infection through the necrotic pathway and required de novo protein synthesis in L929 cells. Subsequent analysis of viral protein expression suggested that axin expression led to suppression of HSV-1-induced premature cell death, resulting in increased late gene expression. In analysis of axin deletion mutants, the regulators of the G-protein signalling (RGS) domain were involved in the axin-mediated enhancement of viral replication and reduction in cell death. These results suggest that viral replication enhancement might be mediated by the axin RGS domain. Show less

no PDF DOI: 10.1099/vir.0.051540-0

AXIN1

Batten disease is linked to altered expression of mitochondria-related metabolic molecules.

Sunyang Kang, Jae Hong Seo, Tae-Hwe Heo +1 more · 2013 · Neurochemistry international · Elsevier · added 2026-04-24

Sunyang Kang, Jae Hong Seo, Tae-Hwe Heo, Sung-Jo Kim Show less

Batten disease (BD)--also known as juvenile neuronal ceroid lipofuscinoses-is an inherited neurodegenerative disorder caused by CLN3 gene mutations. Although CLN3-related oxidative and mitochondrial s Show more

Batten disease (BD)--also known as juvenile neuronal ceroid lipofuscinoses-is an inherited neurodegenerative disorder caused by CLN3 gene mutations. Although CLN3-related oxidative and mitochondrial stresses have been studied in BD, the pathologic mechanism of the disease is not clearly understood. To address the molecular factors linked to high levels of oxidative stress in BD, we examined the expression of mitochondria-related metabolic molecules, including pyruvate dehydrogenase (PDH), ATP citrate lyase (ACL), and phosphoenolpyruvate carboxykinase (PEPCK), as well as the apoptosis-related ganglioside, acetyl-GD3. We observed an increased expression of PDH and a decreased expression of ACL, PEPCK, and acetyl-GD3 in BD lymphoblast cells compared to normal cells, possibly resulting in the high ROS levels, mitochondrial membrane depolarization, and apoptosis typically found in BD. Show less

no PDF DOI: 10.1016/j.neuint.2013.03.007

CLN3

Cell cycle arrest in Batten disease lymphoblast cells.

Sunyang Kang, June-Bum Kim, Tae-Hwe Heo +1 more · 2013 · Gene · Elsevier · added 2026-04-24

Sunyang Kang, June-Bum Kim, Tae-Hwe Heo, Sung-Jo Kim Show less

Batten disease is an inherited neurodegenerative disorder caused by a CLN3 gene mutation. Batten disease is characterized by blindness, seizures, cognitive decline, and early death. Although apoptotic Show more

Batten disease is an inherited neurodegenerative disorder caused by a CLN3 gene mutation. Batten disease is characterized by blindness, seizures, cognitive decline, and early death. Although apoptotic cell death is one of the pathological hallmarks of Batten disease, little is known about the regulatory mechanism of apoptosis in this disease. Since the CLN3 gene is suggested to be involved in the cell cycle in a yeast model, we investigated the cell cycle profile and its regulatory factors in lymphoblast cells from Batten disease patients. We found G1/G0 cell cycle arrest in Batten disease cells, with overexpression of p21, sphingosine, glucosylceramide, and sulfatide as possible cell cycle regulators. Show less

no PDF DOI: 10.1016/j.gene.2013.02.022

CLN3

DNA methylation of MAPK signal-inhibiting genes in papillary thyroid carcinoma.

Eun Kyung Lee, Ki-Wook Chung, Sun Kyung Yang +4 more · 2013 · Anticancer research · added 2026-04-24

Eun Kyung Lee, Ki-Wook Chung, Sun Kyung Yang, Min Ji Park, Hye Sook Min, Seok Won Kim, Han Sung Kang Show less

The purpose of this study was to identify the DNA methylation status of the mitogen-activated protein kinase (MAPK) signal-inhibiting genes dual-specificity phosphatase 4 (DUSP4) and 6 (DUSP6); and se Show more

The purpose of this study was to identify the DNA methylation status of the mitogen-activated protein kinase (MAPK) signal-inhibiting genes dual-specificity phosphatase 4 (DUSP4) and 6 (DUSP6); and serpin peptidase inhibitor A member 5 (SERPINA5) in thyroid cancer. Using 76 papillary thyroid cancer(PTC) tissues and three thyroid cancer cell lines (TPC1, WRO82-1 and XTC), the expression of three genes and DNA methylation were determined by reverse transcription-PCR and methylation-specific PCR. In all cell lines, the expression of DUSP4 and DUSP6 increased; the corresponding gene promoters were unmethylated. However, SERPINA5 gene expression decreased and SERPINA5 DNA was methylated in the TPC1 cell line. With the de-methylating agent 5'-aza-2'-deoxycytidine, SERPINA5 gene expression was restored. In 82.9% of PTC tissues (63/76), the SERPINA5 DNA promoter was methylated, which was associated with a higher v-raf murine sarcoma viral oncogene homolog B1(BRAF) mutation rate in PTC tissues based on multivariate regression (odds ratio=3.573; 95% confidence interval=1.122-11.379; p=0.031). The expression of the MAPK signal-inhibiting gene SERPINA5 decreased in the TPC1 cell line, SERPINA5 expression was regulated by DNA methylation, which was associated with a higher BRAF mutation rate in PTC. Show less

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DUSP6

An interstitial, apparently-balanced chromosomal insertion in the etiology of Langer-Giedion syndrome in an Asian family.

Byung-Joo Min, Jung Min Ko, Myung-Eui Seo +10 more · 2013 · European journal of medical genetics · Elsevier · added 2026-04-24

Byung-Joo Min, Jung Min Ko, Myung-Eui Seo, Jin-Sun Choi, Sun Kyung Oh, Jane Jeon, Eunhyun Kim, Jennifer E Moon, In Ho Choi, Charles Lee, Ok-Hwa Kim, Tae-Joon Cho, Woong-Yang Park Show less

Langer-Giedion syndrome (LGS; MIM 150230), also called trichorhinophalangeal syndrome type II (TRPS2), is a contiguous gene syndrome caused by a one-copy deletion in the chromosome 8q23-q24 region, sp Show more

Langer-Giedion syndrome (LGS; MIM 150230), also called trichorhinophalangeal syndrome type II (TRPS2), is a contiguous gene syndrome caused by a one-copy deletion in the chromosome 8q23-q24 region, spanning the genes TRPS1 and EXT1. We identified an LGS family with two affected and two unaffected siblings from unaffected parents. To investigate the etiology of recurrence of LGS in this family, array CGH was performed on all family members. We identified a 7.29 Mb interstitial deletion at chromosome region 8q23-q24 in the two affected siblings, but no such deletion in the unaffected family members. However, the mother and one of the two unaffected siblings carried a 1.29 Mb deletion at chromosome region 8q24.1, sharing the distal breakpoint with the larger deleted segment found in the affected siblings. Another unaffected sibling had a 6.0 Mb duplication, sharing the proximal breakpoint of the deletion in the affected siblings. Karyotypic and FISH analyses in the unaffected mother revealed an insertional translocation of 8q23-q24 genomic material into chromosome 13: 46,XX,ins(13;8)(q33;q23q24). This insertional translocation in the mother results in the recurrence of LGS in this family, highlighting the importance of submicroscopic rearrangements in the genetic counseling for LGS. Show less

no PDF DOI: 10.1016/j.ejmg.2013.06.011

EXT1

Genome-wide association study of serum albumin:globulin ratio in Korean populations.

Kyung-Won Hong, Hyun-Seok Jin, Daesub Song +3 more · 2013 · Journal of human genetics · Nature · added 2026-04-24

Kyung-Won Hong, Hyun-Seok Jin, Daesub Song, Hye-Kyoung Kwak, Sung Soo Kim, Yeonjung Kim Show less

Low albumin:globulin (A/G) ratios are associated with vascular adverse events, nephrotic syndrome and autoimmune disease. Genome-wide association studies (GWASs) have been identifying genetic variants Show more

Low albumin:globulin (A/G) ratios are associated with vascular adverse events, nephrotic syndrome and autoimmune disease. Genome-wide association studies (GWASs) have been identifying genetic variants associated with total serum protein, serum albumin and globulins, but A/G ratio has never been considered the target phenotype. To identify the genetic basis of the A/G ratio, we performed a GWAS on A/G ratio in 4205 individuals from the Ansan cohort and confirmed the results in 4637 subjects from the Ansung cohort. The single-nucleotide polymorphism (SNP) genotypes of Affymetrix SNP array 5.0 were obtained from the Korean Association Resource Consortium, and we selected 290 659 common SNPs with a minor allele frequency >0.05. Genetic factors for A/G ratio were analyzed by linear regression analysis, controlling for age, sex, body mass index, smoking status and alcohol drinking status as covariates. From the GWAS of the Ansan cohort, we identified two significant genome-wide signals (P-values<5 × 10(-8)) and 36 moderate signals (P-value<1.0 × 10(-4)). These 38 signals were tested in the Ansung population. Eleven SNPs from six loci (GALNT2, IRF4, HLA-DBP1, SLC31A1, FADS1 and TNFRSF13B) were replicated, with P-values<0.05. The most compelling association was observed in the TNFRSF13B locus on chromosome 17p11.2 (SNP: rs4561508), with an overall combined P-value=7.80 × 10(-24). The other significant signal was observed on chromosome 11q12.2-the FADS1 locus (SNP: rs174548)-with an overall combined P-value=3.54 × 10(-8). Show less

no PDF DOI: 10.1038/jhg.2012.130

FADS1

G protein-linked signaling pathways in bipolar and major depressive disorders.

Hiroaki Tomita, Mary E Ziegler, Helen B Kim +15 more · 2013 · Frontiers in genetics · Frontiers · added 2026-04-24

Hiroaki Tomita, Mary E Ziegler, Helen B Kim, Simon J Evans, Prabhakara V Choudary, Jun Z Li, Fan Meng, Manhong Dai, Richard M Myers, Charles R Neal, Terry P Speed, Jack D Barchas, Alan F Schatzberg, Stanley J Watson, Huda Akil, Edward G Jones, William E Bunney, Marquis P Vawter Show less

The G-protein linked signaling system (GPLS) comprises a large number of G-proteins, G protein-coupled receptors (GPCRs), GPCR ligands, and downstream effector molecules. G-proteins interact with both Show more

The G-protein linked signaling system (GPLS) comprises a large number of G-proteins, G protein-coupled receptors (GPCRs), GPCR ligands, and downstream effector molecules. G-proteins interact with both GPCRs and downstream effectors such as cyclic adenosine monophosphate (cAMP), phosphatidylinositols, and ion channels. The GPLS is implicated in the pathophysiology and pharmacology of both major depressive disorder (MDD) and bipolar disorder (BPD). This study evaluated whether GPLS is altered at the transcript level. The gene expression in the dorsolateral prefrontal (DLPFC) and anterior cingulate (ACC) were compared from MDD, BPD, and control subjects using Affymetrix Gene Chips and real time quantitative PCR. High quality brain tissue was used in the study to control for confounding effects of agonal events, tissue pH, RNA integrity, gender, and age. GPLS signaling transcripts were altered especially in the ACC of BPD and MDD subjects. Transcript levels of molecules which repress cAMP activity were increased in BPD and decreased in MDD. Two orphan GPCRs, GPRC5B and GPR37, showed significantly decreased expression levels in MDD, and significantly increased expression levels in BPD. Our results suggest opposite changes in BPD and MDD in the GPLS, "activated" cAMP signaling activity in BPD and "blunted" cAMP signaling activity in MDD. GPRC5B and GPR37 both appear to have behavioral effects, and are also candidate genes for neurodegenerative disorders. In the context of the opposite changes observed in BPD and MDD, these GPCRs warrant further study of their brain effects. Show less

📄 PDF DOI: 10.3389/fgene.2013.00297

GPRC5B

Exome sequencing-driven discovery of coding polymorphisms associated with common metabolic phenotypes.

A Albrechtsen, N Grarup, Y Li +105 more · 2013 · Diabetologia · Springer · added 2026-04-24

A Albrechtsen, N Grarup, Y Li, T Sparsø, G Tian, H Cao, T Jiang, S Y Kim, T Korneliussen, Q Li, C Nie, R Wu, L Skotte, A P Morris, C Ladenvall, S Cauchi, A Stančáková, G Andersen, A Astrup, K Banasik, A J Bennett, L Bolund, G Charpentier, Y Chen, J M Dekker, A S F Doney, M Dorkhan, T Forsen, T M Frayling, C J Groves, Y Gui, G Hallmans, A T Hattersley, K He, G A Hitman, J Holmkvist, S Huang, H Jiang, X Jin, J M Justesen, K Kristiansen, J Kuusisto, M Lajer, O Lantieri, W Li, H Liang, Q Liao, X Liu, T Ma, X Ma, M P Manijak, M Marre, J Mokrosiński, A D Morris, B Mu, A A Nielsen, G Nijpels, P Nilsson, C N A Palmer, N W Rayner, F Renström, R Ribel-Madsen, N Robertson, O Rolandsson, P Rossing, T W Schwartz, D.E.S.I.R. Study Group, P E Slagboom, M Sterner, DIAGRAM Consortium, M Tang, L Tarnow, T Tuomi, E van't Riet, N van Leeuwen, T V Varga, M A Vestmar, M Walker, B Wang, Y Wang, H Wu, F Xi, L Yengo, C Yu, X Zhang, J Zhang, Q Zhang, W Zhang, H Zheng, Y Zhou, D Altshuler, L M 't Hart, P W Franks, B Balkau, P Froguel, M I McCarthy, M Laakso, L Groop, C Christensen, I Brandslund, T Lauritzen, D R Witte, A Linneberg, T Jørgensen, T Hansen, J Wang, R Nielsen, O Pedersen Show less

Human complex metabolic traits are in part regulated by genetic determinants. Here we applied exome sequencing to identify novel associations of coding polymorphisms at minor allele frequencies (MAFs) Show more

Human complex metabolic traits are in part regulated by genetic determinants. Here we applied exome sequencing to identify novel associations of coding polymorphisms at minor allele frequencies (MAFs) >1% with common metabolic phenotypes. The study comprised three stages. We performed medium-depth (8×) whole exome sequencing in 1,000 cases with type 2 diabetes, BMI >27.5 kg/m(2) and hypertension and in 1,000 controls (stage 1). We selected 16,192 polymorphisms nominally associated (p < 0.05) with case-control status, from four selected annotation categories or from loci reported to associate with metabolic traits. These variants were genotyped in 15,989 Danes to search for association with 12 metabolic phenotypes (stage 2). In stage 3, polymorphisms showing potential associations were genotyped in a further 63,896 Europeans. Exome sequencing identified 70,182 polymorphisms with MAF >1%. In stage 2 we identified 51 potential associations with one or more of eight metabolic phenotypes covered by 45 unique polymorphisms. In meta-analyses of stage 2 and stage 3 results, we demonstrated robust associations for coding polymorphisms in CD300LG (fasting HDL-cholesterol: MAF 3.5%, p = 8.5 × 10(-14)), COBLL1 (type 2 diabetes: MAF 12.5%, OR 0.88, p = 1.2 × 10(-11)) and MACF1 (type 2 diabetes: MAF 23.4%, OR 1.10, p = 8.2 × 10(-10)). We applied exome sequencing as a basis for finding genetic determinants of metabolic traits and show the existence of low-frequency and common coding polymorphisms with impact on common metabolic traits. Based on our study, coding polymorphisms with MAF above 1% do not seem to have particularly high effect sizes on the measured metabolic traits. Show less

📄 PDF DOI: 10.1007/s00125-012-2756-1

MACF1

Txnip contributes to impaired glucose tolerance by upregulating the expression of genes involved in hepatic gluconeogenesis in mice.

Seong Ho Jo, Mi Young Kim, Joo Man Park +2 more · 2013 · Diabetologia · Springer · added 2026-04-24

Seong Ho Jo, Mi Young Kim, Joo Man Park, Tae Hyun Kim, Yong Ho Ahn Show less

Thioredoxin-interacting protein (TXNIP) is upregulated in the hyperglycaemic state and represses glucose uptake, resulting in imbalanced glucose homeostasis. In this study, we propose a mechanism of h Show more

Thioredoxin-interacting protein (TXNIP) is upregulated in the hyperglycaemic state and represses glucose uptake, resulting in imbalanced glucose homeostasis. In this study, we propose a mechanism of how TXNIP impairs hepatic glucose tolerance at the transcriptional level. We administered adenoviral Txnip (Ad-Txnip) to normal mice and performed intraperitoneal glucose tolerance tests (IPGTT), insulin tolerance tests (ITT) and pyruvate tolerance tests (PTT). After Ad-Txnip administration, the expression of genes involved in glucose metabolism, including G6pc and Gck, was analysed using quantitative real-time PCR and western blot. To understand the increased G6pc expression in liver resulting from Txnip overexpression, we performed pull-down assays for TXNIP and small heterodimer partner (SHP). Luciferase reporter assays and chromatin immunoprecipitation using the Txnip promoter were performed to elucidate the interrelationship between carbohydrate response element-binding protein (ChREBP) and transcription factor E3 (TFE3) in the regulation of Txnip expression. Overabundance of TXNIP resulted in impaired glucose, insulin and pyruvate tolerance in normal mice. Ad-Txnip transduction upregulated G6pc expression and caused a decrease in Gck levels in the liver of normal mice and primary hepatocytes. TXNIP increased G6pc expression by forming a complex with SHP, which is known to be a negative modulator of gluconeogenesis. Txnip expression in mouse models of diabetes was decreased by Ad-Tfe3 administration, suggesting that TFE3 may play a negative role through competition with ChREBP at the E-box of the Txnip promoter. We demonstrated that TXNIP impairs glucose and insulin tolerance in mice by upregulating G6pc through interaction with SHP. Show less

no PDF DOI: 10.1007/s00125-013-3050-6

MLXIPL

Cooperative transcriptional activation of ATP-binding cassette sterol transporters ABCG5 and ABCG8 genes by nuclear receptors including Liver-X-Receptor.

Su Sun Back, Jinsu Kim, Daehyung Choi +3 more · 2013 · BMB reports · added 2026-04-24

Su Sun Back, Jinsu Kim, Daehyung Choi, Eui Sup Lee, Soo Young Choi, Kyuhyung Han Show less

The ATP-binding cassette transporters ABCG5 and ABCG8 form heterodimers that limit absorption of dietary sterols in the intestine and promote cholesterol elimination from the body through hepatobiliar Show more

The ATP-binding cassette transporters ABCG5 and ABCG8 form heterodimers that limit absorption of dietary sterols in the intestine and promote cholesterol elimination from the body through hepatobiliary secretion. To identify cis-regulatory elements of the two genes, we have cloned and analyzed twenty-three evolutionary conserved region (ECR) fragments using the CMV-luciferase reporter system in HepG2 cells. Two ECRs were found to be responsive to the Liver-X-Receptor (LXR). Through elaborate deletion studies, regions containing putative LXREs were identified and the binding of LXRα was demonstrated by EMSA and ChIP assay. When the LXREs were inserted upstream of the intergenic promoter, synergistic activation by LXRα/RXRα in combination with GATA4, HNF4α, and LRH-1, which had been shown to bind to the intergenic region, was observed. In conclusion, we have identified two LXREs in ABCG5/ABCG8 genes for the first time and propose that these LXREs, especially in the ECR20, play major roles in regulating these genes. Show less

no PDF DOI: 10.5483/bmbrep.2013.46.6.246

NR1H3

An active metabolite of oltipraz (M2) increases mitochondrial fuel oxidation and inhibits lipogenesis in the liver by dually activating AMPK.

Tae Hyun Kim, Jeong Sik Eom, Chan Gyu Lee +3 more · 2013 · British journal of pharmacology · Blackwell Publishing · added 2026-04-24

Tae Hyun Kim, Jeong Sik Eom, Chan Gyu Lee, Yoon Mee Yang, Yong Sup Lee, Sang Geon Kim Show less

Oltipraz, a cancer chemopreventive agent, has an anti-steatotic effect via liver X receptor-α (LXRα) inhibition. Here we have assessed the biological activity of a major metabolite of oltipraz (M2) ag Show more

Oltipraz, a cancer chemopreventive agent, has an anti-steatotic effect via liver X receptor-α (LXRα) inhibition. Here we have assessed the biological activity of a major metabolite of oltipraz (M2) against liver steatosis and steatohepatitis and the underlying mechanism(s). Blood biochemistry and histopathology were assessed in high-fat diet (HFD)-fed mice treated with M2. An in vitroHepG2 cell model was used to study the mechanism of action. Immunoblotting, real-time PCR and luciferase reporter assays were performed to measure target protein or gene expression levels. M2 treatment inhibited HFD-induced steatohepatitis and diminished oxidative stress in liver. It increased expression of genes encoding proteins involved in mitochondrial fuel oxidation. Mitochondrial DNA content and oxygen consumption rate were enhanced. Moreover, M2 treatment repressed activity of LXRα and induction of its target genes, indicating anti-lipogenic effects. M2 activated AMP-activated protein kinase (AMPK). Inhibition of AMPK by over-expression of dominant negative AMPK (DN-AMPK) or by Compound C prevented M2 from inducing genes for fatty acid oxidation and repressed sterol regulatory element binding protein-1c (SREBP-1c) expression. M2 activated liver kinase B1 (LKB1) and increased the AMP/ATP ratio. LKB1 knockdown failed to reverse target protein modulations or AMPK activation by M2, supporting the proposal that both LKB1 and increased AMP/ATP ratio contribute to its anti-steatotic effect. M2 inhibited liver steatosis and steatohepatitis by enhancing mitochondrial fuel oxidation and inhibiting lipogenesis. These effects reflected activation of AMPK elicited by increases in LKB1 activity and AMP/ATP ratio. Show less

no PDF DOI: 10.1111/bph.12057

NR1H3

AMPK connects energy stress to PIK3C3/VPS34 regulation.

Joungmok Kim, Kun-Liang Guan · 2013 · Autophagy · added 2026-04-24

The class III phosphatidylinositol (PtdIns)-3 kinase, PIK3C3/VPS34, forms multiple complexes and regulates a variety of cellular functions, especially in intracellular vesicle trafficking and autophag Show more

The class III phosphatidylinositol (PtdIns)-3 kinase, PIK3C3/VPS34, forms multiple complexes and regulates a variety of cellular functions, especially in intracellular vesicle trafficking and autophagy. Even though PtdIns3P, the product of PIK3C3, is thought to be a critical membrane marker for the autophagosome, it is unclear how PIK3C3 is regulated in response to autophagy-inducing stimuli. A complexity of PIK3C3 biology is due in part to the existence of multiple complexes, of which the ATG14- or UVRAG-containing complexes play important roles in autophagy. We recently discovered differential regulation of distinct PIK3C3 complexes in response to energy starvation and showed a mechanism by which AMPK directly phosphorylates PIK3C3 and BECN1 to regulate non- and pro-autophagic PIK3C3 complexes, respectively. Show less

no PDF DOI: 10.4161/auto.24877

PIK3C3

Homologous expression of γ-glutamylcysteine synthetase increases grain yield and tolerance of transgenic rice plants to environmental stresses.

Yong-Hoe Choe, Young-Saeng Kim, Il-Sup Kim +5 more · 2013 · Journal of plant physiology · Elsevier · added 2026-04-24

Yong-Hoe Choe, Young-Saeng Kim, Il-Sup Kim, Mi-Jung Bae, Eun-Jin Lee, Yul-Ho Kim, Hyang-Mi Park, Ho-Sung Yoon Show less

Various environmental stresses induce reactive oxygen species (ROS), causing deleterious effects on plant cells. Glutathione (GSH), a critical antioxidant, is used to combat ROS. GSH is produced by γ- Show more

Various environmental stresses induce reactive oxygen species (ROS), causing deleterious effects on plant cells. Glutathione (GSH), a critical antioxidant, is used to combat ROS. GSH is produced by γ-glutamylcysteine synthetase (γ-ECS) and glutathione synthetase (GS). To evaluate the functional roles of the Oryza sativa L. Japonica cv. Ilmi ECS (OsECS) gene, we generated transgenic rice plants overexpressing OsECS under the control of an inducible promoter (Rab21). When grown under saline conditions (100mM) for 4 weeks, 2-independent transgenic (TGR1 and TGR2) rice plants remained bright green in comparison to control wild-type (WT) rice plants. TGR1 and TGR2 rice plants also showed a higher GSH/GSSG ratio than did WT rice plants in the presence of 100mM NaCl, which led to enhanced redox homeostasis. TGR1 and TGR2 rice plants also showed lower ion leakage and higher chlorophyll-fluorescence when exposed to 10μM methyl viologen (MV). Furthermore, the TGR1 and TGR2 rice seeds had approximately 1.5-fold higher germination rates in the presence of 200mM salt. Under paddy field conditions, OsECS-overexpression in transgenic rice plants increased rice grain yield (TGW) and improved biomass. Overall, our results show that OsECS overexpression in transgenic rice increases tolerance and germination rate in the presence of abiotic stress by improving redox homeostasis via an enhanced GSH pool. Our findings suggest that increases in grain yield by OsECS overexpression could improve crop yields under natural environmental conditions. Show less

no PDF DOI: 10.1016/j.jplph.2012.12.002

RAB21

Saccharomyces cerevisiae KNU5377 stress response during high-temperature ethanol fermentation.

Il-Sup Kim, Young-Saeng Kim, Hyun Kim +2 more · 2013 · Molecules and cells · Springer · added 2026-04-24

Il-Sup Kim, Young-Saeng Kim, Hyun Kim, Ingnyol Jin, Ho-Sung Yoon Show less

Fuel ethanol production is far more costly to produce than fossil fuels. There are a number of approaches to cost-effective fuel ethanol production from biomass. We characterized stress response of th Show more

Fuel ethanol production is far more costly to produce than fossil fuels. There are a number of approaches to cost-effective fuel ethanol production from biomass. We characterized stress response of thermotolerant Saccharomyces cerevisiae KNU5377 during glucose-based batch fermentation at high temperature (40°C). S. cerevisiae KNU5377 (KNU5377) transcription factors (Hsf1, Msn2/4, and Yap1), metabolic enzymes (hexokinase, glyceraldehyde-3-phosphate dehydrogenase, glucose-6-phosphate dehydrogenase, isocitrate dehydrogenase, and alcohol dehydrogenase), antioxidant enzymes (thioredoxin 3, thioredoxin reductase, and porin), and molecular chaperones and its cofactors (Hsp104, Hsp82, Hsp60, Hsp42, Hsp30, Hsp26, Cpr1, Sti1, and Zpr1) are upregulated during fermentation, in comparison to S. cerevisiae S288C (S288C). Expression of glyceraldehyde-3-phosphate dehydrogenase increased significantly in KNU5377 cells. In addition, cellular hydroperoxide and protein oxidation, particularly lipid peroxidation of triosephosphate isomerase, was lower in KNU5377 than in S288C. Thus, KNU5377 activates various cell rescue proteins through transcription activators, improving tolerance and increasing alcohol yield by rapidly responding to fermentation stress through redox homeostasis and proteostasis. Show less

no PDF DOI: 10.1007/s10059-013-2258-0

ZPR1

Evolutionarily conserved residues at glucagon-like peptide-1 (GLP-1) receptor core confer ligand-induced receptor activation.

Mi Jin Moon, Hee Young Kim, Sumi Park +8 more · 2012 · The Journal of biological chemistry · American Society for Biochemistry and Molecular Biology · added 2026-04-24

Mi Jin Moon, Hee Young Kim, Sumi Park, Dong-Kyu Kim, Eun Bee Cho, Cho Rong Park, Dong-Joo You, Jong-Ik Hwang, Kyungjin Kim, Han Choe, Jae Young Seong Show less

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) play important roles in insulin secretion through their receptors, GLP1R and GIPR. Although GLP-1 and GIP are att Show more

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) play important roles in insulin secretion through their receptors, GLP1R and GIPR. Although GLP-1 and GIP are attractive candidates for treatment of type 2 diabetes and obesity, little is known regarding the molecular interaction of these peptides with the heptahelical core domain of their receptors. These core domains are important not only for specific ligand binding but also for ligand-induced receptor activation. Here, using chimeric and point-mutated GLP1R/GIPR, we determined that evolutionarily conserved amino acid residues such as Ile(196) at transmembrane helix 2, Leu(232) and Met(233) at extracellular loop 1, and Asn(302) at extracellular loop 2 of GLP1R are responsible for interaction with ligand and receptor activation. Application of chimeric GLP-1/GIP peptides together with molecular modeling suggests that His(1) of GLP-1 interacts with Asn(302) of GLP1R and that Thr(7) of GLP-1 has close contact with a binding pocket formed by Ile(196), Leu(232), and Met(233) of GLP1R. This study may provide critical clues for the development of peptide and/or nonpeptide agonists acting at GLP1R. Show less

no PDF DOI: 10.1074/jbc.M111.276808

GIPR

Apolipoprotein A-IV is a novel substrate for matrix metalloproteinases.

Ji Yoon Park, Jun Hyoung Park, Wookju Jang +5 more · 2012 · Journal of biochemistry · Oxford University Press · added 2026-04-24

Ji Yoon Park, Jun Hyoung Park, Wookju Jang, In-Kwan Hwang, In Ja Kim, Hwa-Jung Kim, Kyung-Hyun Cho, Seung-Taek Lee Show less

Screening of matrix metalloproteinase (MMP)-14 substrates in human plasma using a proteomics approach previously identified apolipoprotein A-IV (apoA-IV) as a novel substrate for MMP-14. Here, we show Show more

Screening of matrix metalloproteinase (MMP)-14 substrates in human plasma using a proteomics approach previously identified apolipoprotein A-IV (apoA-IV) as a novel substrate for MMP-14. Here, we show that among the tested MMPs, purified apoA-IV is most susceptible to cleavage by MMP-7, and that apoA-IV in plasma can be cleaved more efficiently by MMP-7 than MMP-14. Purified recombinant apoA-IV (44-kDa) was cleaved by MMP-7 into several fragments of 41, 32, 29, 27, 24, 22 and 19 kDa. N-terminal sequencing of the fragments identified two internal cleavage sites for MMP-7 in the apoA-IV sequence, between Glu(185) and Leu(186), and between Glu(262) and Leu(263). The cleavage of lipid-bound apoA-IV by MMP-7 was less efficient than that of lipid-free apoA-IV. Further, MMP-7-mediated cleavage of apoA-IV resulted in a rapid loss of its intrinsic anti-oxidant activity. Based on the fact that apoA-IV plays important roles in lipid metabolism and possesses anti-oxidant activity, we suggest that cleavage of lipid-free apoA-IV by MMP-7 has pathological implications in the development of hyperlipidemia and atherosclerosis. Show less

no PDF DOI: 10.1093/jb/mvr137

APOA4

👤 Tae-Eun Kim